Reuchlin studied at various universities, specializing in Greek and publishing a Latin lexicon in 1475–76. He then switched to law, obtaining his degree in 1481, and he held court and judicial posts in Württemberg and its capital, Stuttgart, from the 1480s until 1512. Reuchlin was a pioneer in the scientific study of classical Greek and translated many classical texts. In the 1490s he became interested in Hebrew, and in 1506 there appeared his celebrated De Rudimentis Hebraicis (“On the Fundamentals of Hebrew”), a grammar and lexicon that was of great importance in promoting the scientific study of Hebrew and hence of the Old Testament in its original language.

When the Dominicans of Cologne led by Johannes Pfefferkorn succeeded in getting Emperor Maximilian I to order (1509) the destruction of Hebrew books as hostile to Christianity, Reuchlin defended the study and preservation of Hebrew literature. The Dominican inquisitor Jacob Hochstraten began procedures against Reuchlin himself in 1513, and in response Reuchlin appealed to Pope Leo X. As the dispute went on, the entire European liberal and humanist community aligned itself on Reuchlin’s side against the Dominicans, and in 1516 a papal commission acquitted Reuchlin of heresy. The controversy occasioned the Epistolae obscurorum virorum (1515; “Letters of the Obscure Men”), a satirical pamphlet by young humanists that mercilessly ridiculed late scholasticism as represented by the Dominicans. But interest in the controversy was soon displaced by the shift of public attention to Martin Luther and his clash with the Roman Catholic church.

Reuchlin was second only to Desiderius Erasmus among German humanists and was the most important German teacher of Greek and Hebrew in his day. Though his stand in the Hebrew-literature controversy had proven beneficial to the Protestant cause, Reuchlin repudiated his nephew, Philip Melanchthon, and Luther in their separation from Roman Catholicism.